The threat of an intentional or unintentional spread of poxvirus infections to a vulnerable population has led to increased efforts to find safe, rapidly deployable treatments against such infections. Vaccination is now being offered to some healthcare workers and other first responders. Previously reported smallpox vaccine-associated adverse reactions, along with the unknown prevalence of risk factors among today's population has prompted the preparation of guidance for clinicians in evaluating and treating patients with smallpox vaccination complications. Following this guidance, the vaccine is not recommended for those with eczema and other exfoliative skin disorders, those with hereditary or acquired immunodeficiencies, or for pregnant women (Keith et al., Antimicrobial Agents and Chemotherapy, May 2004, p. 1869-1871). Also, the Centers for Disease Control issued a health advisory recommending as a precautionary measure that persons with known cardiac disease not be vaccinated at this time (CDC Health Advisory, Mar. 26, 2003).
Cidofovir (CDV) and cyclic CDV (cCDV) have been shown to be potent inhibitors of poxvirus, but are inactive when given orally. The synthesis of cidofovir is described in U.S. Pat. No. 5,142,051, issued Aug. 25, 1992. Enhanced activity over the parent compound has been observed using lipid prodrugs such as hexadecyloxypropyl (HDP) and octadecyloxyethyl (ODE) derivatives of CDV and cCDV (HDP-CDV, HDP-cCDV, ODE-CDV and ODE-cCDV). The synthesis of lipid prodrugs of CDV and cCDV is described, for example, in U.S. Pat. No. 6,716,825, issued Apr. 26, 2004. The antiviral activity of alkoxyalkyl and alkyl esters of cidofovir against human and murine cytomegalovirus is described in Wan et al., Antimicrobial Agents and Chemotherapy, 49:656-662 (2005).
Due to the seriousness of the disease, there is a need for new therapies in the event of a poxvirus outbreak or in the event of complications that may occur in the use of vaccination. There is a need for compositions and methods for effectively treating poxvirus infections.
Therefore, it is an object of the invention to provide new methods and compositions for the treatment of poxvirus.